An enzyme is an organic catalyst produced by living cells but capable of acting independently. They are complex proteins which are capable of inducing chemical changes in other substances without being changed themselves in the process.
Enzymes are found particularly in digestive juices acting upon food substances, causing them to break down into simpler compounds. They are capable of accelerating greatly the speed of chemical reactions.
The reactions effected by the digestive enzymes are chiefly decompositions of a hydrolic nature, but enzymes are equally important in the synthetic reactions of assimilation.
The substance acted upon by an enzyme is called the substrate. Zymogen is the name given to the precursor of an enzyme. The more common groups of enzymes are: Hydrolytic enzymes; fat-, protein-, starch-, and sugar-splitting enzymes; coagulating enzymes or those which cause clotting, such as rennin or thrombin; oxidases or oxidizing enzymes deamidizing enzymes, those which are important in removing amines or amino groups during oxidation; reductases or reducing enzymes; splitting enzymes; joining enzymes, and those in the active form such as trypsin which promote clotting.
The physiological function of the proteolytic enzymes in digestion of proteins is well known, their action being to split proteins into amino acids and peptides. Hence they have long been administered orally for digestive purposes in cases of pancreatic deficiency, see example "Entozyme", Pacific Drug Review, July 1959, page 66, and Merck Index, 6th ediction, Merck & Co., Inc., Rahway, November 1952, page 981.
Proteolytic enzymes have been demonstrated to be effective therapeutics in reducing inflammation and edema when properly administered. It is theorized that trypsin functions as a depolymerase at the site of inflammation to reverse the fibrogen-fibrin reaction responsible for the inflammation. As the porosity of the protein network wall is increased, the intercellular fluid is released, hydrostatic pressures are reduced, capillaries open, and circulation in the local area is restored. Thus the anti-inflammatory action of trypsin is a direct result of its facilitating drainage from the inflamed area by lysis of fibrin plugs in the lymphatics and capillaries about the inflammatory lesion.
It is known that trypsin, chymotrypsin and some proteolytic enzymes can be administered intramuscularly and are effective in reducing inflammation. In U.S. Pat. No. 3,004,893 to Julius Martin, Oct. 12, 1961, there is disclosed an enteric coated trypsin and chymotrypsin anti-inflammatory composition which may be administered orally to obtain systemic absorption of these proteolytic enzymes from the ileum. The enteric coating is of such a composition that it will not break down until the tablet or capsule reaches the ileum. While such compositions are suitable as an anti-inflammatory treatment, they are not considered suitable for anti-tumor treatment.
U.S. Pat. No. 3,940,478 to Leonard D. Kirtz, Feb. 24, 1976, discloses the use of proteolytic enzymes in the active forms to facilitate contact of an antibiotic with the bacteria of a wound. As described therein the proteolytic enzyme works on the film of proteinaceous coagulum that the body tends to form on the surface of open wounds to disrupt or otherwise break it down thereby permitting access of the antibiotic to the shielded bacteria. While such method of utilizing proteolytic enzymes in their active form as adjuncts to antibiotics is suitable for topical applications to open wounds, such method is not disclosed as suitable for in vivo treatment of tumor cells.
One of the most distressing characteristics of cancer is the apparent failure of the body's immune system to combat the run-away tumor cells. The cancer tumor seems remarkably to elude, or delude, the natural defenses of immunological surveillance that manage to ward off most other diseases. It is believed that cancer tumors may avoid the body's normal defenses by growing a "protective shell" formed out of substances secreted by the growths themselves. Normally, the body's defense mechanism would recognize certain proteins, for example, on the surface of the tumor cells and attack them, but the protective shell made of a substance called fibrin gel gets in the way and may be the reason immunotherapy is limited. It is also believed that, ordinarily, when fibrin begins to form in tissue, as it would in healing, it attracts certain disease fighting cells. However, the cancerous tumor is believed to secrete another substance called microphage - migration inhibitor that wards off any cells destructive to the tumor. While little is known about the mechanisms by which tumor cells elude immunologic surveillance, it is desirable to provide a process of treating such tumors to render them susceptible to immunological surveillance, whereby regression is effected and/or tumor growth inhibited or reduced. It is also a desirable object to provide a therapeutic composition which will sufficiently decompose the shell of cancer tumors to permit the natural immunological system to take over.